CORR Insights^®: The Alpha-defensin Test for Periprosthetic Joint Infection is Not Affected by Prior Antibiotic Administration

Where Are We Now?

Despite advances in the algorithms and the availability of investigations used to diagnose periprosthetic joint infection (PJI), challenges in obtaining the correct diagnosis remain. The major and minor criteria, as outlined by the Musculoskeletal Infection Society (MSIS), are a useful tool to diagnose the majority of infected total hip and knee replacements [8]. Additional investigations not yet part of the MSIS criteria have been developed and show promising results in obtaining an accurate diagnosis. In 2014, Deirmengian et al. [3] published the evolving use of biomarkers for the investigation of patients with potential PJI. Synovial alpha defensin 1 is one such biomarker that shows accurate results, with nearly 100% sensitivity and specificity [1, 2, 4].

Alpha defensin, a peptide secreted by neutrophils in response to the presence of a pathogen, interacts with the pathogen’s cell membrane causing cell death; therefore it has antimicrobial activities [5]. The alpha-defensin test is an immunoassay that measures the concentration of alpha defensin in synovial fluid. While highly accurate, the alpha-defensin test can be falsely positive in the presence of metallosis [2]. The addition of synovial C-reactive protein (CRP) can distinguish between septic and aseptic failure in this subgroup of patients. Synovial CRP seems to be unaffected by metallosis, and a low synovial CRP (< 3.0 mg/L) helps exclude the presence of coexisting infection in cases of metallosis [2].

It is well recognized that antibiotic use can negatively affect traditional investigations for PJI, resulting in false negative cultures, inflammatory markers, and synovial while blood cell counts. Some favorable data on the accuracy of alpha defensin with concurrent antibiotic use has been published as part of a larger study [2]. However, the authors of the current study are the first to review a larger number of patients with PJI on antibiotics to determine the diagnostic accuracy of alpha defensin, as well as compare the results of alpha defensin to traditional investigations in this subgroup of patients. Shahi and colleagues found that alpha defensin remains a sensitive test for diagnosing PJI even in the presence of antibiotics. As in previous studies, the sensitivity remained at 100%, and the absolute levels of synovial alpha defensin were not clinically different between the antibiotic and nonantibiotic group. The study also showed a statistical difference in CRP, synovial fluid white blood cell count, and percentage of neutrophils in patients on antibiotics versus those not taking antibiotics.

Where Do We Need To Go?

Shahi and colleagues excluded acute infection (symptoms < 4 weeks) from their study with the rationale that synovial and serological markers are not reliable during this time period. Additional information on alpha defensin in acute infections, with patients both on and off antibiotics, would be of interest as this group of patients can be a diagnostic challenge. These patients are often erroneously started on antibiotics before a proper work-up is completed.

What is also surprising from their paper is the number of patients with PJI who were on antibiotics at the time of referral to orthopaedic surgeons for investigation and management of patients with potential PJI. Just more than a quarter (28%) were on antibiotics. This highlights the need for improved education of primary providers who care for patients that present with painful joint replacements.

The alpha-defensin test has established itself as a valuable tool to determine the presence or absence of infection. Additional data on the diagnostic accuracy of alpha defensin in specific arthropathies such as gout and pseudogout and systemic inflammatory conditions would also be helpful. Crystalline arthropathies can be present in joint replacements and may mimic PJI as traditional tests are often positive, however true infection may coexist making diagnosis difficult. Additionally, information specifically on the performance of alpha defensin in low-grade infections (Propionibacterium acnes, coagulase negative Staphylococcus) would be of value to the clinician.

How Do We Get There?

The alpha-defensin biomarker provides us with only a yes or no answer and if yes, it does not identify the organism. Such identification is critical to successful management of patients with PJI. The next phase of investigations for improved diagnostic capabilities of PJI needs to focus on molecular methods of pathogen identification that are unaffected by antibiotics or comorbidities. Detection of bacteria using electrophoretic impedance measurement may be one method that holds promise for the future [6, 7].